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Avastin is a monoclonal antibody to vascular endothelial growth factor (VEGF), first approved for use in combination with 5-fluorouracil in the treatment of metastatic colorectal cancer.  This approval was based upon a single primary efficacy study which included 923 patients.  The clinical endpoint was survival.

In contrast, the accelerated approval for treatment of Metastatic Breast Cancer (MBC), was based upon clinical study of 722 patients and had an endpoint of progression free survival (PFS).  The approval is for use in combination with paclitaxel.  While this study did not show an effect on overall survival, the median PFS time was 11.3 months compared to 5.8 months with paclitaxel along. However, during the original approval for MBS the reviewer stated, “It is noted that the magnitude of the treatment effect on  PFS is uncertain given the significant amount of missing data…..Confirmation of clinical benefit may be based on an analysis of the ongoing phase 3 studies.” 

This is not unusual for an accelerated approval, there are typically post approval studies designed to either validate the selected clinical surrogate marker, collect additional safety data or confirm the efficacy data in larger ongoing studies. Unlike other products recently removed from the market, the issue for Avastin is not the safety profile,  at question is the efficacy of the product. 

The accelerated approval contained a post-approval commitment for two additional  phase 3 studies  These studies were namesd AVADO and RIBBON1.  It is now CDER’s contention that these studies, completed in 2009 failed to support claimed efficacy. Needless to say Genentech does not agree and requested a hearing.

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